Keratinocyte growth factor protects endometrial cells from oxygen glucose deprivation/re-oxygenation via activating Nrf2 signaling.

Oxygen and glucose deprivation (OGD)-re-oxygenation (OGDR) exposure to endometrial cells mimics ischemia-reperfusion injury. The present study tests the potential effect of keratinocyte growth factor (KGF) on the process. We show that KGF receptor KGFR is expressed in human endometrial T-HESC cells and primary murine endometrial cells. KGF pre-treatment protected endometrial cells from OGDR, inhibiting cell viability reduction and cell death. KGF attenuated OGDR-induced programmed necrosis in endometrial cells. Significantly, KGF activated Nrf2 signaling, causing Nrf2 Ser-40 phosphorylation, protein stabilization, nuclear translocation to promote anti-oxidant gene (HO1, NOQ1 and GCLC) expression. Nrf2 silencing (by targeted shRNAs) or CRISPR/Cas9 knockout almost abolished KGF-induced endometrial cell protection against OGDR. Furthermore, KGF activated Akt-mTOR signaling in endometrial cells. Whereas Akt-mTOR inhibitors (LY294002, AZD2014 and RAD001) abolished KGF-induced Nrf2 activation and anti-OGDR cytoprotection. Together, KGF protects endometrial cells from OGDR via activating Akt-mTOR-Nrf2 signaling.

Anti-inflammatory and Antioxidant Effects of Pyrroloquinoline Quinone in L-NAME-Induced Preeclampsia-Like Rat Model.

Preeclampsia (PE) is a pregnancy complication commonly characterized by high blood pressure. Although it is generally believed that the placenta is the root cause of PE, the exact pathogenesis is unknown; consequently, there is no standard clinical treatment. Therefore, it is necessary to explore new therapeutic drugs. Several studies have reported that pyrroloquinoline quinone (PQQ) exhibits anti-inflammatory and antioxidative effects. The purpose of this study was to investigate the protective effect of PQQ diet supplementation on PE-like rat models. L-NAME induced PE-like model rats were intraperitonially administrated with PQQ. The results showed that PQQ significantly improved clinical manifestations and pregnancy outcomes of PE-like rats. The levels of related inflammatory and antioxidant markers were also significantly reversed. A mechanism study showed that PQQ may achieve the above therapeutic effects by inhibiting NF-κB and promoting Nrf2 antioxidant pathways. In conclusion, we showed the protective effect of PQQ on PE-like model rats, by improving anti-inflammation and antioxidation effect through the NF-κB-Nrf2 pathway.

Decreased circUBAP2 Expression Is Associated with Preeclampsia by Limiting Trophoblast Cell Proliferation and Migration.

Preeclampsia (PE) is a common obstetric disease and a major cause of maternal, newborn, and fetal death. This condition is a multisystem disorder characterized by hypertension, proteinuria, and involvement of the kidney, liver, and nervous system. It is generally believed that the placenta is the main cause of PE. circRNAs are a special class of noncoding RNAs that can form covalently closed continuous ring structures with tissue-specific conservation, and they have been reported to play a wide range of regulatory functions in various diseases, including PE. In this study, we reported a novel circUBAP2 (hsa_circ_0003496) and found that it was downregulated in placental tissues from patients with PE compared to healthy controls. After knocking down circUBAP2 in trophoblast cells, we found that cell proliferation and migration were significantly suppressed. In addition, preliminary mechanistic studies showed that circUBAP2 can sponge miR-1244, and FOXM1 was identified as a target gene for miR-1244. Cotransfection of si-circUBAP2 and a miR-1244 inhibitor partially reversed the suppressive effect induced by circUBAP2 depletion on proliferation and migration. In conclusion, the circUBAP2/miR-1244/FOXM1 axis might be a promising molecular marker for the diagnosis and treatment of PE.